The candidate has had 3 years of experience as a clinical veterinarian in infectious disease research in nonhuman primates. She is currently responsible for clinical management of all monkeys involved in SIV research at the Delta Primate Center. A 2 year pilot study has been completed by the candidate in which infants were surgically delivered from females infected with SIV during gestation. These results have been published and the candidate now wishes to continue these studies while improving her skill as an independent investigator with the support of a SERCA grant. We propose to utilize the SIV-infected macaque to identify factors involved in the pathogenesis of placental, and ultimately fetal, infection. During year 1, 24 mature female rhesus monkeys will be infected with SIV 1 month prior to conception to coordinate fetal infection with gestation. Twelve infants will be surgically delivered 10 days prior to term and 12 will undergo vaginal delivery to asses the contribution of parturition on infection. The clinical, virological, and immunological status of infected females and handreared neonates will be evaluated by clinical examination, assessment of antigenemia and viremia, evaluation of changes in lymphocyte subsets, antibody responses, virus-specific proliferative responses, MHC- restricted cytotoxic responses, antibody-dependent cellular cytotoxicity, and natural killer cell activity, respectively. All infants will be evaluated for virus infection by in vitro culture of PBL, detection of viral sequences by PCR amplification, and for SIV-specific immunoglobulin expression. All placentas will be examined by histopathology, immunohistochemistry, and in situ hybridization, as well as in vitro culture and PCR to identify virus-induced changes in the maternal-fetal barrier responsible for fetal infection. In year 3, placental and fetal tissues will be surgically removed from females at timed intervals during gestation to determine the exact gestational stage at which fetal infection occurs and to identify the clinical and immunological factors which predispose toward infection. In the event that no infants become infected with SIV, fetuses will be devoted to the evaluation of chemotherapeutic and vaccine strategies that may center fetal protection to the infant. The DRPRC is a fully equipped primate research facility with complete virology, immunology, and pathology laboratories actively involved in SIV research. A new primate housing facility devoted exclusively to SIV research with an infectious disease nursery and caging for 500 SIV-infected primates is included. Monkeys and related supplies will be provided through an existing grant. Both primary (Dr. Michael Murphey-Corb) and secondary (Dr. Gary Baskin) mentors have agreed to train and guide the candidate in her research training. Immunologists Drs L. Martin and S. Ohkawa have agreed to perform flow cytometric analysis and CMI assays for these studies.